Cai T Y, Zhu Z P, Xu C R, Ji X, Lv T D, Guo Z K, Lin J
Department of Urology, Peking University First Hospital; Institute of Urology, Peking University; National Urological Can-cer Center, Beijing 100034, China.
Beijing Da Xue Xue Bao Yi Xue Ban. 2022 Aug 18;54(4):628-635. doi: 10.19723/j.issn.1671-167X.2022.04.008.
To investigate the expression of fibroblast growth factor receptor 2 () in clear cell renal cell carcinoma (ccRCC; or kidney renal clear cell carcinoma, KIRC), to analyze the relationship between the expression of and the clinical pathological features and prognosis of ccRCC, to study the relationship between the expression of FGFR2 and other molecules, and to explore its role in the development of ccRCC.
Gene expressional and clinical information of ccRCC patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus(GEO) database. Next, the data were transformed and collated. In the study, 104 clinical ccRCC samples and corresponding paracancerous normal tissue samples were collected from Department of Urology, Peking University First Hospital. Immunohistochemistry (IHC) was performed and the staining results were scored, so as to compare the expression of in ccRCC and paracancerous normal tissues. Besides, quantify real-time polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression level of in normal renal epithelial cell lines (293) and ccRCC cell lines (786-O, 769-P, OSRC-2, Caki-1, ACHN, and A498). In addition, the relationship between expression and clinical pathological characteristics (including TNM staging and pathological grading) and survival prognosis in ccRCC patients was further analyzed. Furthermore, the relationship between expression and B cells, T cells, natural killer (NK) cells and neutrophil infiltration in the ccRCC patients was analyzed, and the Biological General Repository for Interactionh Datasets (BioGRID) was used to builds protein-protein interaction (PPI) networks to study molecules that interacted with the FGFR2 protein.
In the TCGA database, the expression of was down-regulated in ccRCC tissue samples compared with normal tissue samples, and the expression in the GEO database also showed this differences. Furthermore, expression was downregulated in ccRCC clinical samples and ccRCC cell lines, compared with corresponding paracancerous normal tissue or normal renal epithelial cell lines. In addition, high expression was associated with earlier, lower-level ccRCC and was associated with a better prognosis in the patients with ccRCC. Moreover, expression was not significantly related to B cells, T cells, NK cells and neutrophil infiltration, and the PPI network showed that FGFR2 protein interacted with certain molecules.
Our work sheds light on the potential role of in the development of ccRCC, suggesting that may serve as a prognostic marker and potential therapeutic target for patients with ccRCC.
探讨成纤维细胞生长因子受体2（FGFR2）在肾透明细胞癌（ccRCC；或肾肾透明细胞癌，KIRC）中的表达，分析FGFR2表达与ccRCC临床病理特征及预后的关系，研究FGFR2表达与其他分子的关系，探讨其在ccRCC发生发展中的作用。
从癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）下载ccRCC患者的基因表达和临床信息。接下来，对数据进行转换和整理。本研究从北京大学第一医院泌尿外科收集了104例临床ccRCC样本及相应的癌旁正常组织样本。进行免疫组织化学（IHC）检测并对染色结果进行评分，以比较FGFR2在ccRCC和癌旁正常组织中的表达。此外，采用定量实时聚合酶链反应（qRT-PCR）检测正常肾上皮细胞系（293）和ccRCC细胞系（786-O、769-P、OSRC-2、Caki-1、ACHN和A498）中FGFR2的mRNA表达水平。另外，进一步分析FGFR2表达与ccRCC患者临床病理特征（包括TNM分期和病理分级）及生存预后的关系。此外，分析FGFR2表达与ccRCC患者中B细胞、T细胞、自然杀伤（NK）细胞和中性粒细胞浸润的关系，并利用生物相互作用数据集通用库（BioGRID）构建蛋白质-蛋白质相互作用（PPI）网络，以研究与FGFR2蛋白相互作用的分子。
在TCGA数据库中，与正常组织样本相比，ccRCC组织样本中FGFR2的表达下调，GEO数据库中的表达也显示出这种差异。此外，与相应的癌旁正常组织或正常肾上皮细胞系相比，FGFR2在ccRCC临床样本和ccRCC细胞系中的表达下调。另外，FGFR2高表达与早期、低级别ccRCC相关，且与ccRCC患者的较好预后相关。此外，FGFR2表达与B细胞、T细胞、NK细胞和中性粒细胞浸润无明显相关性，PPI网络显示FGFR2蛋白与某些分子相互作用。
我们的工作揭示了FGFR2在ccRCC发生发展中的潜在作用，提示FGFR2可能作为ccRCC患者的预后标志物和潜在治疗靶点。
